Obvious differences exist in the propensiy of various individuals to contract glomerulopathies, and genetic variability is often cited as a factor in this regard. Animal models of glomerulopathies also reflect the important role of genetics in species- and strain-related susceptibility to naturally occurring glomerulopathies, or to inducement of experimental glomerulopathies. Despite the importance of this aspect of pathogenesis of renal disease, little attention has been focused on models capable of studying the immunogenetics of experimental renal disease. We propose to examine genetic influences on the pathogenesis of three reproducible types of glomerulopathy in the mouse, a species with extensively studied genetic traits and many inbred strains. We will study the strain variability involved in the pathogenesis of: (a) nephrotoxic nephritis - induced with heterologous rabbit antibody to mouse kidney antigen, (b) autoimmune glomerulotubular nephropathy - a unique subtyped of Steblay autoimmune nephritis described in this laboratory, and (c) chronic immune complex nephropathy - produced by repeated injections of horse-spleen ferritin. Strains of mice will be selected on the basis of their known immune response patterns to certain antigens, incidence of spontaneous nephropathy, individual genetic anomalies of immune responsiveness, and differences in H-2 haplotype. We will monitor: 1) kidney histologic changes using light, electron and immunofluorescence microscopy, 2) antibody response to the immunogen, and 3) alterations of clinical renal function. It is anticipated that these studies will provide insight into the role of genetics in the pathogenesis of experimental immune glomerular disease and provide direction for future studies on the role of genetics in human immune renal disease.